The present invention relates to a method of determining human hereditary disease risk factors, a method of determining hereditary cancer patterns presenting in cancer family histories, and a method of determining whether a cancer family history represents a hereditary pattern.
Recognition of the role of heredity in cancer has increased steadily over time and is discussed in Lynch et al. Genetic Epidemiology of Cancer, Boca Raton: CRC Press, (1989). For example, Lynch et al., Surg. Clin. Of NA, 70:753-774, (1990) has estimated that approximately 9% of carcinoma of the breast is consistent with hereditary breast cancer, and an additional 15-20% will be clearly familial. In addition, the potential for gene testing to confirm hereditary cancer has escalated in recent years, with the discovery of genes that cause breast cancer, colon cancer, and several other cancer syndromes. However mass testing of the population with dozens of expensive gene tests is not viable. The most effective way to identify hereditary cancer families has been with a detailed and accurate cancer family tree. It has been noted, that "[a] thoroughly compiled family history of cancer harbors the potential of being the most cost beneficial component of the patient's workup" (Lynch, H T, "Cancer and the family history trail, New York State Journal of Medicine, pp. 145-147, April, 1991). From such a family tree, the patterns of hereditary cancer can be detected by expert clinical oncologists. Subsequently proper surveillance and management may then be ascertained in concert with judicious gene testing, if and when available, to confirm the risk evaluation.
Unfortunately physicians generally do not take a detailed cancer family history. One study found that in most cases, "the family history of cancer had either been omitted altogether or reported as negative, despite substantial evidence to the contrary" (Lynch, H T et al. Family history in an oncology clinic: Implications for cancer genetics," J. AMA; 242:1268-1272, 1979.). Documentation of the failure to apply proper genetic principles or to obtain necessary family cancer histories has been repeatedly obtained.
Hereditary cancer pattern recognition has been difficult, given that: 1) there are now over 200 types of hereditary cancer syndromes, 2) the family history relayed from the patient can be "fuzzy" and imprecise, and 3) the variation among all the patterns may have billions of different presentations.
In the development of expert systems to mimic clinical experts, experts are studied, and guesses or observations are made as to what rules they are applying for specific cases. This process of study may or may not find or recognize rules, is dependent upon the reporting of the expert, and does not automatically create any rule set, but is dependent upon the insights of an observer. It is observer-dependent, not data-dependent. In addition, such construction and validation can require very long periods of time. Since the hereditary cancer field is constantly changing with new patterns uncovered, an expert system may be obsolete by the time it is developed. In addition, usually any one expert does not have the expertise to cover all the known hereditary cancer syndromes, but combining a version of one rule set from one expert with another rule set from another expert may yield inconsistent results. Finally and perhaps most important, any one expert's rule set is just that: the opinion of one expert. There are different philosophies in medicine as to what issues should be factored in, leading to dissension and confusion.